Formula and preparation method of external patch for easing pain, clearing damp, expelling toxin and losing weight

Abstract

The invention relates to an external patch formula for easing pain, clearing damp, expelling toxin and losing weight and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine, the external patch formula is formed by combining a backing layer, a plaster layer and an anti-sticking layer, the plaster layer is formed by mixing components for easing pain and clearing damp, functionalized beta-cyclodextrin, a stabilizer and a cross-linking agent according to the mass ratio of (12-16): (8-10): (2.0-2.4): (2.8-3.2); functionalized beta-cyclodextrin is used as a medicine layer, the functionalized beta-cyclodextrin contains a beta-cyclodextrin structure, a flexible long-chain alkane structure, a salicylic acid structure and bamboo charcoal powder, the beta-cyclodextrin structure can enhance the transdermal absorption capacity of components capable of easing pain and clearing damp, the flexible long-chain alkane structure can enhance the fat solubility of active components, and therefore the effect of easing pain and clearing damp is achieved. The salicylic acid structure can cooperate with the active components to play the analgesic and anti-inflammatory effects, the bamboo charcoal powder can cooperate with the beta-cyclodextrin to improve the damp-clearing and toxin-expelling capacity and can accelerate moisture metabolism, and through the combined action of the components, the analgesic, damp-clearing and weight-losing effects are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine. Specifically, it relates to an external patch formula for analgesia, dampness removal, detoxification, and weight loss, as well as a production method thereof. Background Art

[0002] Compared with ointments, patches have attracted wide attention due to their advantages such as long-acting, high operational convenience, and low side effects. There are a variety of traditional Chinese medicine patches on the current market, covering various types such as weight loss patches and dampness removal patches. However, their efficacy performances are not satisfactory, and there are generally problems of single function and poor effect. On the one hand, these patches are often designed for a single symptom or need. For example, weight loss patches only focus on promoting fat metabolism, and dampness removal patches only emphasize removing moisture in the body, making it difficult to cope with the complex and changeable health conditions of modern people. On the other hand, since traditional Chinese medicine patches act through skin penetration, restricted by factors such as the skin barrier and drug absorption rate, their drug effects are difficult to fully exert, resulting in the effect being less than expected.

[0003] Chinese Patent Application CN115531505B discloses a traditional Chinese medicine gel patch for anti-inflammatory analgesia of osteoarthritis and its preparation method, including a backing layer, a paste layer, and a release liner; the paste layer is a gel layer formed by a traditional Chinese medicine composition and a matrix for loading the traditional Chinese medicine composition; the traditional Chinese medicine composition includes 15 - 18 parts of vitex trifolia, 15 - 18 parts of cortex cercidis, 3 - 5 parts of angelica sinensis, 3 - 5 parts of chaenomeles speciosa, 3 - 5 parts of salvia miltiorrhiza, 3 - 5 parts of radix paeoniae rubra, 3 - 5 parts of atractylodes lancea, 3 - 5 parts of curcuma zedoaria, 3 - 5 parts of heracleum hemsleyanum, 3 - 5 parts of notopterygium incisum, 3 - 5 parts of trichosanthes kirilowii, 3 - 5 parts of cyathula officinalis, 3 - 5 parts of clematis chinensis, 3 - 5 parts of stephania tetrandra, 3 - 5 parts of ledebouriella seseloides, 3 - 5 parts of strychnos nux-vomica, 2 - 3 parts of ligusticum wallichii, 2 - 3 parts of gentiana macrophylla, 2 - 3 parts of forsythia suspensa, and 1 - 2 parts of glycyrrhiza uralensis. The matrix includes glycerol, EDTA, glycollate aluminum, sodium polyacrylate, water, EM - 178, AC - 10H, a penetration enhancer, a preservative, and tartaric acid. The prepared gel patch has advantages such as convenient use, controllable drug dosage, good adhesiveness, continuous efficacy, and good skin followability. However, the above drug components cannot penetrate through the patch to act on subcutaneous fat and visceral fat, decompose fat cells, and reduce fat accumulation, resulting in poor therapeutic effects of the traditional Chinese medicine gel patch on obese patients.

[0004] Therefore, providing an external patch formula for analgesia, dampness removal, detoxification, and weight loss is a technical problem that needs to be solved currently. Summary of the Invention

[0005] In order to solve the technical problems mentioned in the background art, the present invention provides an external patch formula for analgesia, dampness removal, detoxification, and weight loss, as well as a production method thereof.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] An external patch formula for relieving pain, removing dampness, expelling toxins and losing weight, which is composed of a backing layer, a plaster layer and a non-stick layer. The plaster layer is mixed by analgesic and dampness-removing components, functionalized β-cyclodextrin, a stabilizer and a crosslinking agent according to a mass ratio of 12-16:8-10:2.0-2.4:2.8-3.2;

[0008] The preparation method of the external patch for relieving pain, removing dampness, expelling toxins and losing weight includes the following steps:

[0009] Step S1: After heating and melting the hot melt pressure-sensitive adhesive, add the plaster layer, and then add a transdermal absorption promoter, stir and spread to obtain a paste. Among them, the mass ratio of the hot melt pressure-sensitive adhesive, the plaster layer and the transdermal absorption promoter is 900-1000:160-180:40-60;

[0010] Step S2: Uniformly coat the paste prepared in step S1 on the non-stick layer, then cover it with the backing layer, cool, cut to size, and obtain the external patch for relieving pain, removing dampness, expelling toxins and losing weight.

[0011] Preferably, the transdermal absorption promoter is azone.

[0012] Preferably, the stabilizer is ascorbic acid or Tween-80.

[0013] Preferably, the crosslinking agent is genipin.

[0014] Preferably, the analgesic and dampness-removing components include raw materials and a matrix. The raw materials are composed of the following raw materials in parts by mass: 30-50 parts of Salvia miltiorrhiza, 24-28 parts of Heracleum hemsleyanum, 22-27 parts of Plantago asiatica, 18-24 parts of Atractylodes lancea, 16-22 parts of Piper kadsura, 20-25 parts of Lotus leaf, 11-13 parts of Mentha haplocalyx, 12-14 parts of Myrrh, 5-9 parts of Speranskia tuberculata and 6-8 parts of Sargassum;

[0015] Preferably, the raw materials are composed of the following raw materials in parts by mass: 40 parts of Salvia miltiorrhiza, 26 parts of Heracleum hemsleyanum, 24.5 parts of Plantago asiatica, 21 parts of Atractylodes lancea, 19 parts of Piper kadsura, 22.5 parts of Lotus leaf, 12 parts of Mentha haplocalyx, 13 parts of Myrrh, 7 parts of Speranskia tuberculata and 7 parts of Sargassum.

[0016] Preferably, the matrix includes 600-800 parts of sesame oil and 70-90 parts of xanthan gum.

[0017] Preferably, the matrix includes 700 parts of sesame oil and 80 parts of xanthan gum.

[0018] Preferably, the preparation method of the analgesic and dampness-removing components adopts the following technical scheme:

[0019] A preparation method of analgesic and dampness-removing components includes the following steps:

[0020] Step A1, grinding plantain, atractylodes, cyperus rotundus, lotus leaf, mint, myrrh, radix spatholobi and seaweed together to obtain a mixed powder;

[0021] Step A2: taking 50-80% of the mixed powder by weight and extracting it with anhydrous ethanol and deionized water in turn, concentrating, drying and pulverizing to obtain a mixed extract;

[0022] Step A3, simmer sesame oil to 120-140°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder and the remaining mixed powder while stirring, continue stirring until the system temperature is below 40°C, add angelica dahurica powder and the mixed extract, mix evenly, cool, and obtain the analgesic and dampness-relieving component.

[0023] Preferably, the specific operation steps of step A2 are as follows:

[0024] Take 50-80% of the weight of the mixed medicinal powder and add anhydrous ethanol to reflux extract 1-3 times, combine the ethanol extract, add deionized water to the extracted medicinal residue and reflux extract 1-3 times, combine the water extract, reduce the pressure and concentrate the ethanol extract and the water extract to recover the solvent, concentrate to a thick paste with a relative density of 1.30-1.34 at 80°C, dry at 60-80°C, and then grind into 100-150 meshes to obtain a mixed extract, wherein the mass ratio of the mixed medicinal powder, anhydrous ethanol and deionized water is 1:30-40:20-30.

[0025] Preferably, the mixed drug powder in step A1 is sieved through a 100-150 mesh sieve.

[0026] Preferably, the functionalized β-cyclodextrin is prepared by the following steps:

[0027] Step B1, adding β-cyclodextrin to N, N-dimethylformamide, stirring evenly at 35-45°C, adjusting the pH value to 9-11, dripping a mixture of octenyl succinic anhydride and isopropanol, heating to 85-95°C, continuing to stir and react for 4-6h, adjusting the pH value to 6-7, washing, recrystallizing, and drying to obtain modified β-cyclodextrin, wherein the mass ratio of β-cyclodextrin, N, N-dimethylformamide and the mixture a is 3-6:50-60:0.8-1.2, and the mass ratio of octenyl succinic anhydride and isopropanol in the mixture a is 1-2:10-20. In the above reaction process, the hydroxyl group at the C6 position in the β-cyclodextrin structure reacts with the octenyl succinic anhydride, and a hydrocarbon long chain is introduced through modification, thereby improving the viscosity of the β-cyclodextrin. At the same time, an unsaturated double bond is introduced on the outside of the cyclodextrin, which can participate in the subsequent reaction process;

[0028] Step B2: Dissolve the modified β-cyclodextrin and para-aminosalicylic acid in anhydrous DMF, heat up to 42 - 46 °C, and while stirring, dropwise add the mixed solution b of N,N'-dicyclohexylcarbodiimide, 4-dimethylaminopyridine, and anhydrous DMF. After dropping, heat up to 72 - 78 °C and stir for reaction for 3 - 5 h. After the reaction ends, carry out suction filtration, washing, and drying to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, ultrasonically disperse it evenly, add the bamboo charcoal alcohol solution, stir and mix for 14 - 16 h, centrifuge, wash the precipitate, and dry to obtain the functionalized β-cyclodextrin; wherein, the mass ratio of the modified β-cyclodextrin, para-aminosalicylic acid, anhydrous DMF, and the mixed solution b is 5 - 7:0.2 - 0.4:60 - 70:30 - 40. In the mixed solution b, the mass ratio of N,N'-dicyclohexylcarbodiimide, 4-dimethylaminopyridine, and anhydrous DMF is 0.8 - 1.2:0.54 - 0.66:16 - 20. The mass ratio of the phenylated β-cyclodextrin, anhydrous DMF, and the bamboo charcoal alcohol solution is 4 - 5:46 - 50:26 - 32. The bamboo charcoal alcohol solution is prepared by ultrasonically dispersing bamboo charcoal powder and an ethanol aqueous solution according to a mass ratio of 1:12 - 16, and the mass fraction of the ethanol aqueous solution is 20 - 50%. In the above reaction process, using anhydrous DMF as the solvent, N,N'-dicyclohexylcarbodiimide as the dehydrating agent, 4-dimethylaminopyridine as the acylating agent, the carboxyl group on the modified β-cyclodextrin and the amino group on para-aminosalicylic acid undergo an amidation reaction to obtain the functional component.

[0029] Compared with the prior art, the present invention has the following beneficial effects: The external patch formula for relieving pain, removing dampness, expelling toxins, and losing weight proposed in this application uses salvia miltiorrhiza, angelica pubescens, plantain herb, atractylodes lancea, kadsura pepper stem, lotus leaf, mint, myrrh, divaricate saposhnikovia root, and seaweed as raw materials, and uses sesame oil and xanthan gum as the matrix. The formula components are simple and the action mechanism is clear; by decocting the sesame oil over a slow fire to 120 - 140 °C, adding xanthan gum, turning off the fire after the xanthan gum melts, adding the salvia miltiorrhiza powder and the remaining mixed medicinal powder, continuously stirring until the system temperature is lower than 40 °C, then adding the angelica pubescens powder and the mixed extract to mix evenly, and cooling to obtain the required pain-relieving and dampness-removing components. The preparation method is simple, can significantly improve the dissolution rate of the active pharmaceutical ingredients, improve the bioavailability of the active pharmaceutical ingredients, and does not require combining with other treatment means, and has significant pain-relieving and dampness-removing effects.

[0030] The analgesic and dampness-removing components proposed in this application contain a variety of active ingredients. Among them, Salvia miltiorrhiza, Heracleum hemsleyanum, Plantago asiatica, and Atractylodes lancea are used as the monarch drugs. Salvia miltiorrhiza has the effects of promoting blood circulation to remove blood stasis, dredging meridians and relieving pain, and can relieve inflammation-related pain; Heracleum hemsleyanum has anti-inflammatory, analgesic, and meridians-dredging effects. It not only contains components such as volatile oils and coumarins, which can inhibit the inflammatory response, but also can promote blood circulation and accelerate the metabolism of dampness; Plantago asiatica has the effects of detoxifying and relieving pain, clearing heat and promoting diuresis. It can not only reduce the release of inflammatory mediators such as prostaglandins to play an analgesic role, but also promote the excretion of dampness from urine and has the effect of removing dampness and detoxifying; Atractylodes lancea has the effects of anti-inflammatory, spasmolysis, and promoting diuresis to reduce edema. It can not only dispel wind-damp pathogens in the meridians and improve joint pain caused by poor qi and blood circulation, but also promote the metabolism of water and dampness by enhancing the transportation and transformation function of the spleen to achieve the effect of removing dampness and detoxifying. Piper kadsura and Nelumbo nucifera are used as ministerial drugs. The anti-inflammatory, analgesic, and microcirculation-improving effects of Piper kadsura can enhance the effects of the monarch drugs, strengthen the effects of dispelling wind-dampness and dredging meridians, and improve the analgesic effect; the diuretic, detoxifying, antioxidant, and lipid-lowering effects of Nelumbo nucifera can enhance the effects of the monarch drugs, promote fat decomposition, reduce cholesterol in the body, and promote the excretion of toxins and dampness in the body. Mentha haplocalyx and Myrrha are used as adjuvant drugs. Mentha haplocalyx contains menthol, which can not only relieve the burning or stinging sensation to play an analgesic role, but also act as a penetration enhancer to enhance the transdermal absorption of the diuretic traditional Chinese medicine components in Plantago asiatica to support the role of the monarch drugs; Myrrha has the effects of promoting blood circulation to remove blood stasis and dispelling wind and removing dampness. It can not only promote blood flow, disperse stasis caused by dampness blockage, relieve joint pain, but also indirectly enhance the dampness-removing effect by improving microcirculation and accelerating the metabolism of dampness. Speranskia tuberculata and Sargassum fusiforme are used as messenger drugs. Speranskia tuberculata has the effects of targeted analgesia and microcirculation improvement. It can not only promote local blood circulation, accelerate inflammatory metabolism, and relieve pain caused by wind-cold-damp pathogens or blood stasis, but also guide the medicinal effects of the monarch drugs and ministerial drugs directly to the affected parts such as joints and muscles to enhance the analgesic effect. Sargassum fusiforme has the effects of multi-target analgesia and targeted dampness-removing. It not only has the effect of promoting diuresis to reduce edema, can promote urine excretion, relieve edema and dampness, and relieve pain caused by dampness blockage, but also can guide the medicinal effects of the monarch drugs and ministerial drugs directly to the affected parts such as phlegm retention and edema to enhance the analgesic and dampness-removing effects; taking Speranskia tuberculata and Sargassum fusiforme together as messenger drugs can make the formula components work synergistically, ensure the targeting and effectiveness of the drug, and improve the analgesic and dampness-removing effects.

[0031] The analgesic and dampness-removing components proposed in this application use sesame oil and xanthan gum as the matrix. Sesame oil is rich in various unsaturated fatty acids and vitamins (such as vitamin E), and its good permeability and moisturizing property can not only help the analgesic and dampness-removing components penetrate deep into the skin, improve the analgesic and dampness-removing effects, but also promote the liquid metabolism of the subcutaneous tissue, accelerate the discharge of damp pathogens, and achieve the effect of removing dampness; as a microbial polysaccharide, xanthan gum can absorb the excess oil and metabolic waste on the skin, achieving the effect of removing dampness and detoxifying. The two together as the matrix have a moderate viscosity, making the paste easy to apply and absorb. It can form a protective film on the skin surface, providing a good release environment for the analgesic and dampness-removing components, while preventing external stimulation and water loss, and protecting the wound from contamination.

[0032] The external patch formula proposed in this application uses functionalized β-cyclodextrin as the drug layer. The functionalized β-cyclodextrin contains a β-cyclodextrin structure, a flexible long-chain alkane structure, a salicylic acid structure, and bamboo charcoal powder.

[0033] The presence of the β-cyclodextrin structure can enhance the transdermal absorption ability of the analgesic and dampness-removing components. The presence of the flexible long-chain alkane structure can enhance the liposolubility of the active ingredients in the analgesic and dampness-removing components through hydrophobic interaction. The salicylic acid structure can cooperate with the active ingredients in the analgesic and dampness-removing components to play a local analgesic and anti-inflammatory role through skin penetration. The presence of bamboo charcoal powder can not only cooperate with the β-cyclodextrin structure to adsorb the metabolic waste and impurities on the skin surface, improving the ability of removing dampness and detoxifying, but also promote blood circulation and accelerate the metabolism of dampness. Detailed implementation manners

[0034] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0035] The salvia miltiorrhiza powder is produced by Shaanxi Yiruinong Biotechnology Co., Ltd., with the specification of tanshinone IIA 5%. The angelica pubescens powder is produced by Xi'an Jinheng Chemical Co., Ltd., with the brand of Xi'an Jinheng and the product number of JH65565642. The hot-melt pressure-sensitive adhesive is the Yuexing brand acrylate pressure-sensitive adhesive produced by Foshan Nanhai Xin'an Pearl River Chemical Industry Co., Ltd., with the execution standard of ZJ-20180101. The anti-adhesive layer is the medical anti-adhesive isolation release paper provided by Cangnan Hengtai Paper Products Factory. The backing layer is the white blank plaster patch produced by Yangzhou Bestcare Medical Technology Co., Ltd., with the specification of 5*5 cm. Other raw materials not mentioned in this application are all commercially available.

[0036] Preparation Examples 1-3 and Comparative Preparation Examples 1-3 provide a kind of functionalized β-cyclodextrin.

[0037] Preparation Example 1

[0038] This preparation example provides a functionalized β-cyclodextrin, which is prepared by the following steps:

[0039] Step B1: Add β-cyclodextrin into N,N-dimethylformamide, control the rotation speed at 620 rpm at 35 °C, stir for 12 min until homogeneous, adjust the pH value to 9 with saturated sodium carbonate aqueous solution, dropwise add a mixed solution a of octenyl succinic anhydride and isopropanol. After dropping, raise the temperature to 85 °C, keep the rotation speed unchanged, continue to stir and react for 4 h, then adjust the pH value to 6 with saturated citric acid aqueous solution, wash 3 times with deionized water without removing, recrystallize, and dry at 60 °C to constant weight to obtain modified β-cyclodextrin. Among them, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and mixed solution a is 3:50:0.8. In the mixed solution a, the mass ratio of octenyl succinic anhydride and isopropanol is 1:10;

[0040] Step B2: Dissolve the modified β-cyclodextrin and p-aminosalicylic acid in anhydrous DMF, raise the temperature to 42 °C, control the rotation speed at 600 rpm, dropwise add a mixed solution b of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF while stirring. After dropping, raise the temperature to 72 °C, keep the rotation speed unchanged, continue to stir and react for 3 h. After the reaction, filter by suction, wash the filter cake 3 times with anhydrous ethanol and deionized water, and dry at 64 °C to constant weight to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, control the ultrasonic frequency at 40 kHz, the ultrasonic power at 600 w, ultrasonic for 12 min until homogeneous, add the bamboo charcoal alcohol solution, stir and mix at a rotation speed of 600 rpm for 14 h, centrifuge, wash the precipitate 3 times with anhydrous ethanol and deionized water in sequence, and dry at 60 °C to constant weight to obtain the functionalized β-cyclodextrin; among them, the mass ratio of modified β-cyclodextrin, p-aminosalicylic acid, anhydrous DMF and mixed solution b is 5:0.2:60:30. In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 0.8:0.54:16. The mass ratio of phenylated β-cyclodextrin, anhydrous DMF and bamboo charcoal alcohol solution is 4:46:26. The bamboo charcoal alcohol solution is prepared by ultrasonic dispersion of bamboo charcoal powder and ethanol aqueous solution according to the mass ratio of 1:12, and the mass fraction of the ethanol aqueous solution is 20%.

[0041] Preparation Example 2

[0042] This preparation example provides a functionalized β-cyclodextrin, which is prepared by the following steps:

[0043] Step B1: Add β-cyclodextrin into N,N-dimethylformamide, control the rotation speed at 660 rpm at 35 °C, stir for 16 min until homogeneous, adjust the pH value to 10 with saturated sodium carbonate aqueous solution, dropwise add the mixed solution a of octenyl succinic anhydride and isopropanol. After dropping, raise the temperature to 90 °C, keep the rotation speed unchanged, continue to stir and react for 5 h, then adjust the pH value to 6.5 with saturated citric acid aqueous solution, wash 4 times with deionized water without removing ions, recrystallize, and dry at 64 °C to constant weight to obtain modified β-cyclodextrin. Among them, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and the mixed solution a is 4.5:55:1.0. In the mixed solution a, the mass ratio of octenyl succinic anhydride and isopropanol is 1.5:15;

[0044] Step B2: Dissolve the modified β-cyclodextrin and p-aminosalicylic acid in anhydrous DMF, raise the temperature to 44 °C, while stirring, dropwise add the mixed solution b of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF. After dropping, raise the temperature to 75 °C, stir and react for 4 h. After the reaction is completed, filter, wash and dry to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, control the ultrasonic frequency at 35 kHz, ultrasonic power at 550 w, ultrasonic for 18 min until homogeneous, add the bamboo charcoal alcohol solution, stir and mix at a rotation speed of 640 rpm for 15 h, centrifuge, and wash the precipitate 4 times with anhydrous ethanol and deionized water in sequence, and dry at 65 °C to constant weight to obtain the functionalized β-cyclodextrin; among them, the mass ratio of the modified β-cyclodextrin, p-aminosalicylic acid, anhydrous DMF and the mixed solution b is 6:0.3:65:35. In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 1.0:0.60:18. The mass ratio of the phenylated β-cyclodextrin, anhydrous DMF and the bamboo charcoal alcohol solution is 4.5:48:28. The bamboo charcoal alcohol solution is prepared by ultrasonic dispersion of bamboo charcoal powder and ethanol aqueous solution according to a mass ratio of 1:14, and the mass fraction of the ethanol aqueous solution is 35%.

[0045] Preparation Example 3

[0046] This preparation example provides a functionalized β-cyclodextrin, which is prepared by the following steps:

[0047] Step B1: Add β-cyclodextrin into N,N-dimethylformamide, control the rotation speed at 700 rpm at 45 °C, stir for 20 min until uniform, adjust the pH value to 11 with saturated sodium carbonate aqueous solution, dropwise add the mixed solution a of octenyl succinic anhydride and isopropanol. After dropping, raise the temperature to 95 °C, keep the rotation speed unchanged, continue to stir and react for 6 h, adjust the pH value to 7 with 1.2 M hydrochloric acid aqueous solution, wash, recrystallize, and dry to obtain modified β-cyclodextrin. Among them, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and the mixed solution a is 6:60:1.2. In the mixed solution a, the mass ratio of octenyl succinic anhydride and isopropanol is 2:20;

[0048] Step B2: Dissolve the modified β-cyclodextrin and p-aminosalicylic acid in anhydrous DMF, raise the temperature to 46 °C, while stirring, dropwise add the mixed solution b of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF. After dropping, raise the temperature to 78 °C, control the rotation speed at 780 rpm, stir and react for 5 h. After the reaction is completed, perform suction filtration. The filter cake is washed 5 times successively with anhydrous ethanol and deionized water, and dried at 60 °C to constant weight to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, control the ultrasonic frequency at 30 kHz, the ultrasonic power at 500 w, and ultrasonicate for 20 min until uniform. Add the bamboo charcoal alcohol solution, stir and mix at a rotation speed of 680 rpm for 16 h, centrifuge, and the precipitate is washed 5 times successively with anhydrous ethanol and deionized water, and dried at 70 °C to constant weight to obtain functionalized β-cyclodextrin; Among them, the mass ratio of the modified β-cyclodextrin, p-aminosalicylic acid, anhydrous DMF and the mixed solution b is 7:0.4:70:40. In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 1.2:0.66:20. The mass ratio of phenylated β-cyclodextrin, anhydrous DMF and the bamboo charcoal alcohol solution is 5:50:32. The bamboo charcoal alcohol solution is prepared by ultrasonic dispersion of bamboo charcoal powder and ethanol aqueous solution according to the mass ratio of 1:16, and the mass fraction of the ethanol aqueous solution is 50%.

[0049] Comparative Preparation Example 1

[0050] This comparative preparation example provides a functionalized β-cyclodextrin, which is prepared by the following steps:

[0051] Step B1: Add β-cyclodextrin into N,N-dimethylformamide, control the rotation speed at 620 rpm at 35°C, stir for 12 min until homogeneous, adjust the pH value to 9 with saturated sodium carbonate aqueous solution, dropwise add the mixed solution a of itaconic anhydride and isopropanol. After dropping, raise the temperature to 85°C, keep the rotation speed unchanged, continue to stir and react for 4 h, then adjust the pH value to 6 with saturated citric acid aqueous solution, wash 3 times with deionized water without removing ions, recrystallize, and dry at 60°C to constant weight to obtain modified β-cyclodextrin. Among them, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and the mixed solution a is 3:50:0.8. In the mixed solution a, the mass ratio of itaconic anhydride and isopropanol is 1:10;

[0052] Step B2: Dissolve the modified β-cyclodextrin and p-aminosalicylic acid in anhydrous DMF, raise the temperature to 42°C, and dropwise add the mixed solution b of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF while stirring. After dropping, raise the temperature to 72°C, stir and react for 3 h. After the reaction is completed, filter, wash and dry to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, ultrasonically disperse it evenly, add the bamboo charcoal alcohol solution, stir and mix for 14 h, centrifuge, wash and dry the precipitate to obtain functionalized β-cyclodextrin; among them, the mass ratio of the modified β-cyclodextrin, p-aminosalicylic acid, anhydrous DMF and the mixed solution b is 5:0.2:60:30. In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 0.8:0.54:16. The mass ratio of the phenylated β-cyclodextrin, anhydrous DMF and the bamboo charcoal alcohol solution is 4:46:26. The bamboo charcoal alcohol solution is prepared by ultrasonically dispersing bamboo charcoal powder and ethanol aqueous solution according to the mass ratio of 1:12, and the mass fraction of the ethanol aqueous solution is 20%.

[0053] Comparative Preparation Example 2

[0054] This comparative preparation example provides a functionalized β-cyclodextrin, which is prepared by the following steps:

[0055] Step B1: Add β-cyclodextrin into N,N-dimethylformamide, control the rotation speed at 620 rpm at 35°C, stir for 12 min until homogeneous, adjust the pH value to 9 with saturated sodium carbonate aqueous solution, dropwise add the mixed solution a of octenyl succinic anhydride and isopropanol. After dropping, raise the temperature to 85°C, keep the rotation speed unchanged, continue to stir and react for 4 h, then adjust the pH value to 6 with saturated citric acid aqueous solution, wash 3 times with deionized water without removing ions, recrystallize, and dry at 60°C to constant weight to obtain modified β-cyclodextrin. Among them, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and the mixed solution a is 3:50:0.8. In the mixed solution a, the mass ratio of octenyl succinic anhydride and isopropanol is 1:10;

[0056] Step B2: Dissolve the modified β-cyclodextrin and glycine in anhydrous DMF, heat up to 42°C, control the rotation speed at 600 rpm, and while stirring, dropwise add the mixed solution b of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF. After dropping, heat up to 72°C, maintain the rotation speed unchanged, and continue stirring and reacting for 3 h. After the reaction is completed, perform suction filtration. The filter cake is washed 3 times with anhydrous ethanol and deionized water, and dried to constant weight at 64°C to obtain phenylated β-cyclodextrin. Add the phenylated β-cyclodextrin into anhydrous DMF, control the ultrasonic frequency at 40 kHz, the ultrasonic power at 600 w, and ultrasonicate for 12 min until uniform. Then add the bamboo charcoal alcohol solution, stir and mix at a rotation speed of 600 rpm for 14 h, centrifuge, and the precipitate is washed 3 times with anhydrous ethanol and deionized water successively, and dried to constant weight at 60°C to obtain the functionalized β-cyclodextrin; wherein, the mass ratio of the modified β-cyclodextrin, glycine, anhydrous DMF and the mixed solution b is 5:0.2:60:30. In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 0.8:0.54:16. The mass ratio of the phenylated β-cyclodextrin, anhydrous DMF and the bamboo charcoal alcohol solution is 4:46:26. The bamboo charcoal alcohol solution is prepared by ultrasonic dispersion of bamboo charcoal powder and ethanol aqueous solution according to a mass ratio of 1:12, and the mass fraction of the ethanol aqueous solution is 20%.

[0057] Preparation Examples 4-6 and Comparative Preparation Examples 3-5 provide an analgesic and dampness-removing component.

[0058] Preparation Example 4

[0059] This preparation example provides an analgesic and dampness-removing component, which includes a raw material medicine and a matrix. The raw material medicine is composed of the following raw materials in parts by mass: 30 parts of Salvia miltiorrhiza, 24 parts of Heracleum hemsleyanum, 22 parts of Plantago asiatica, 18 parts of Atractylodes lancea, 16 parts of Piper kadsura, 20 parts of Lotus leaf, 11 parts of Mentha haplocalyx, 12 parts of Myrrha, 5 parts of Speranskia tuberculata and 6 parts of Sargassum; the matrix includes 600 parts of sesame oil and 70 parts of xanthan gum.

[0060] The preparation method of this analgesic and dampness-removing component includes the following steps:

[0061] Step A1: Coarsely powder Plantago asiatica, Atractylodes lancea, Piper kadsura, Lotus leaf, Mentha haplocalyx, Myrrha, Speranskia tuberculata and Sargassum together, and pass through a 100-mesh sieve to obtain a mixed medicinal powder.

[0062] Step A2: Take 50% by mass of the mixed medicinal powder and reflux extract it once with anhydrous ethanol. Combine the ethanol extracts. Add deionized water to the residue after extraction and reflux extract it once. The dosage of anhydrous ethanol each time is 12 times the mass of 50% of the mixed medicinal powder, and the dosage of deionized water each time is 14 times the mass of the residue. The reflux time of anhydrous ethanol each time is 30 minutes, and the reflux time of deionized water each time is 24 minutes. Combine the water extracts. After concentrating the ethanol extract and the water extract under reduced pressure to recover the solvent, concentrate it to a thick paste with a relative density of 1.30 at 80°C, dry it at 60°C, and pulverize it into 100 mesh to obtain the mixed extract.

[0063] Step A3: Decoct the sesame oil over a slow fire until it reaches 120°C, add xanthan gum, turn off the fire after the xanthan gum melts, and while stirring at a speed of 75 rpm, add the salvia powder and the remaining mixed medicinal powder. Continue stirring until the system temperature reaches 35°C, then add the angelica pubescens powder and the mixed extract and mix evenly. Cool to obtain the analgesic and dampness-removing component.

[0064] Preparation Example 5

[0065] This preparation example provides an analgesic and dampness-removing component, including a raw material medicine and a matrix. The raw material medicine is composed of the following raw materials in parts by mass: 40 parts of salvia, 26 parts of angelica pubescens, 24.5 parts of plantain herb, 21 parts of atractylodes rhizome, 19 parts of caulis piperis kadsurae, 22.5 parts of lotus leaf, 12 parts of mint, 13 parts of myrrh, 7 parts of divaricate saposhnikovia root, and 7 parts of seaweed; the matrix includes 700 parts of sesame oil and 80 parts of xanthan gum.

[0066] The preparation method of this analgesic and dampness-removing component includes the following steps:

[0067] Step A1: Coarsely powder the plantain herb, atractylodes rhizome, caulis piperis kadsurae, lotus leaf, mint, myrrh, divaricate saposhnikovia root, and seaweed together, and sieve through a 125-mesh sieve to obtain the mixed medicinal powder.

[0068] Step A2: Take 65% by mass of the mixed medicinal powder and reflux extract it twice with anhydrous ethanol. Combine the ethanol extracts. Add deionized water to the residue after extraction and reflux extract it twice. The dosage of anhydrous ethanol each time is 14 times the mass of 65% of the mixed medicinal powder, and the dosage of deionized water each time is 16 times the mass of the residue. The reflux time of anhydrous ethanol each time is 45 minutes, and the reflux time of deionized water each time is 28 minutes. Combine the water extracts. After concentrating the ethanol extract and the water extract under reduced pressure to recover the solvent, concentrate it to a thick paste with a relative density of 1.32 at 80°C, dry it at 70°C, and pulverize it into 125 mesh to obtain the mixed extract.

[0069] Step A3: Decoct the sesame oil over a slow fire until it reaches 130°C, add xanthan gum, turn off the fire after the xanthan gum melts, and while stirring at a speed of 78 rpm, add the salvia powder and the remaining mixed medicinal powder. Continue stirring until the system temperature reaches 37°C, then add the angelica pubescens powder and the mixed extract and mix evenly. Cool to obtain the analgesic and dampness-removing component.

[0070] Preparation Example 6

[0071] This preparation example provides an analgesic and dehumidifying component, including a raw material and a matrix, wherein the raw material is composed of the following raw materials in parts by weight: 50 parts of salvia miltiorrhiza, 28 parts of angelica dahurica, 27 parts of plantain, 24 parts of atractylodes, 22 parts of kadzu vine, 25 parts of lotus leaf, 13 parts of mint, 14 parts of myrrh, 9 parts of scutellaria baicalensis and 8 parts of seaweed; the matrix includes 800 parts of sesame oil and 90 parts of xanthan gum;

[0072] The preparation method of the analgesic and dehumidifying component comprises the following steps:

[0073] Step A1, grinding plantain, atractylodes, spatholobi, lotus leaf, mint, myrrh, radix spatholobi and seaweed together, and passing through a 150-mesh sieve to obtain a mixed powder;

[0074] Step A2, taking 80% of the mass of the mixed powder and adding anhydrous ethanol to reflux extraction for 3 times, combining the ethanol extracts, adding deionized water to the extracted medicinal residues for reflux extraction for 3 times, each time the amount of anhydrous ethanol is 16 times the mass of the 80% mixed medicinal powder, each time the amount of deionized water is 18 times the mass of the medicinal residues, each time the anhydrous ethanol reflux time is 1h, each time the deionized water reflux time is 32min, combining the water extracts, concentrating the ethanol extract and the water extract under reduced pressure to recover the solvent, concentrating to a thick paste with a relative density of 1.34 at 80°C, drying at 80°C and then crushing into 150 meshes to obtain a mixed extract;

[0075] Step A3, simmer sesame oil to 140°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder and the remaining mixed powder at a speed of 81 rpm while stirring, continue stirring until the system temperature reaches 39°C, add angelica dahurica powder and the mixed extract, mix evenly, and cool to obtain the analgesic and dehumidifying component.

[0076] Comparative Preparation Example 3

[0077] This comparative preparation example provides an analgesic and dehumidifying component. Compared with Preparation Example 4, the lotus leaf in Preparation Example 4 is replaced with an equal mass of Piper mesenteriae, an analgesic and dehumidifying component, including a raw material and a matrix, the raw material is composed of the following raw materials in parts by mass: 30 parts of Salvia miltiorrhiza, 24 parts of Angelica dahurica, 22 parts of Plantago, 18 parts of Atractylodes macrocephala, 36 parts of Piper mesenteriae, 11 parts of Menthus officinalis, 12 parts of Myrrha, 5 parts of Herba spatholobi and 6 parts of Seaweed; the matrix includes 600 parts of sesame oil and 70 parts of xanthan gum;

[0078] The preparation method of the analgesic and dehumidifying component comprises the following steps:

[0079] Step A1, grinding plantain, atractylodes, spatholobi, mint, myrrh, radix spatholobi and seaweed together, and passing through a 100-mesh sieve to obtain a mixed powder;

[0080] Step A2, taking 50% of the mass of the mixed powder and adding anhydrous ethanol to reflux extract once, combining the ethanol extract, adding deionized water to the extracted medicinal residue and reflux extracting once, the amount of anhydrous ethanol used each time is 12 times the mass of the 50% mixed medicinal powder, the amount of deionized water used each time is 14 times the mass of the medicinal residue, the anhydrous ethanol reflux time each time is 30 minutes, and the deionized water reflux time each time is 24 minutes, combining the water extract, concentrating the ethanol extract and the water extract under reduced pressure to recover the solvent, concentrating to a thick paste with a relative density of 1.30 at 80°C, drying at 60°C and then crushing into 100 meshes to obtain a mixed extract;

[0081] Step A3, simmer sesame oil to 120°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder and the remaining mixed powder at a speed of 75 rpm while stirring, continue stirring until the system temperature reaches 35°C, add angelica dahurica powder and the mixed extract, mix evenly, and cool to obtain the analgesic and dehumidifying component.

[0082] Comparative Preparation Example 4

[0083] This comparative preparation example provides an analgesic and dehumidifying component. Compared with Preparation Example 4, the mint in Preparation Example 4 is replaced with an equal mass of myrrh. An analgesic and dehumidifying component includes a raw material and a matrix. The raw material is composed of the following raw materials in parts by mass: 30 parts of salvia miltiorrhiza, 24 parts of angelica dahurica, 22 parts of plantain, 18 parts of atractylodes, 16 parts of kadzu vine, 20 parts of lotus leaf, 23 parts of myrrh, 5 parts of scutellaria baicalensis and 6 parts of seaweed; the matrix includes 600 parts of sesame oil and 70 parts of xanthan gum;

[0084] The preparation method of the analgesic and dehumidifying component comprises the following steps:

[0085] Step A1, grinding plantain, atractylodes, kelp, lotus leaf, myrrh, radix spatholobi and seaweed together, and passing through a 100-mesh sieve to obtain a mixed powder;

[0086] Step A2, taking 50% of the mass of the mixed powder and adding anhydrous ethanol to reflux extract once, combining the ethanol extract, adding deionized water to the extracted medicinal residue and reflux extracting once, the amount of anhydrous ethanol used each time is 12 times the mass of the 50% mixed medicinal powder, the amount of deionized water used each time is 14 times the mass of the medicinal residue, the anhydrous ethanol reflux time each time is 30 minutes, and the deionized water reflux time each time is 24 minutes, combining the water extract, concentrating the ethanol extract and the water extract under reduced pressure to recover the solvent, concentrating to a thick paste with a relative density of 1.30 at 80°C, drying at 60°C and then crushing into 100 meshes to obtain a mixed extract;

[0087] Step A3, simmer sesame oil to 120°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder and the remaining mixed powder at a speed of 75 rpm while stirring, continue stirring until the system temperature reaches 35°C, add angelica dahurica powder and the mixed extract, mix evenly, and cool to obtain the analgesic and dehumidifying component.

[0088] Comparative Preparation Example 5

[0089] This comparative preparation example provides an analgesic and dehumidifying component. Compared with Preparation Example 4, all the mixed powder is extracted, specifically:

[0090] A pain-relieving and dampness-removing ingredient, comprising a raw material medicine and a matrix, wherein the raw material medicine is composed of the following raw materials in parts by weight: 30 parts of salvia miltiorrhiza, 24 parts of angelica dahurica, 22 parts of plantain, 18 parts of atractylodes, 16 parts of kadzu vine, 20 parts of lotus leaf, 11 parts of mint, 12 parts of myrrh, 5 parts of scutellaria baicalensis and 6 parts of seaweed; the matrix comprises 600 parts of sesame oil and 70 parts of xanthan gum;

[0091] The preparation method of the analgesic and dehumidifying component comprises the following steps:

[0092] Step A1, grinding plantain, atractylodes, spatholobi, lotus leaf, mint, myrrh, radix spatholobi and seaweed together, and passing through a 100-mesh sieve to obtain a mixed powder;

[0093] Step A2, taking all the mixed powders and adding anhydrous ethanol to reflux extract once, combining the ethanol extracts, adding deionized water to the extracted drug residues and reflux extracting once, the amount of anhydrous ethanol used each time is 12 times the mass of 50% of the mixed powders, the amount of deionized water used each time is 14 times the mass of the drug residues, the anhydrous ethanol reflux time is 30 minutes each time, and the deionized water reflux time is 24 minutes each time, combining the water extracts, concentrating the ethanol extracts and the water extracts under reduced pressure to recover the solvent, concentrating to a thick paste with a relative density of 1.30 at 80°C, drying at 60°C and then crushing into 100 meshes to obtain a mixed extract;

[0094] Step A3, simmer sesame oil to 120°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder at a speed of 75 rpm while stirring, continue stirring until the system temperature reaches 35°C, add angelica dahurica powder and the mixed extract, mix evenly, and cool to obtain the analgesic and dehumidifying component.

[0095] Examples 1-3 and Comparative Examples 1-4 provide a formulation of an external patch for relieving pain, removing dampness, detoxifying and reducing weight.

[0096] Example 1

[0097] This embodiment provides a formula for an external patch for analgesia, dampness removal, detoxification, and weight loss, which is composed of a backing layer, a plaster layer, and a non-stick layer. The plaster layer is formed by mixing the analgesic and dampness-removing components prepared in Preparation Example 4, the functionalized β-cyclodextrin prepared in Preparation Example 1, ascorbic acid, and genipin in a mass ratio of 12:8:2.0:2.8;

[0098] Step S1: After the hot-melt pressure-sensitive adhesive is heated and melted, the plaster layer is added, and then azone is added. After stirring, it is spread. Among them, the mass ratio of the hot-melt pressure-sensitive adhesive, the plaster layer, and azone is 900:160:40;

[0099] Step S2: The paste prepared in Step S1 is evenly coated on the non-stick layer, and the coating thickness is controlled to be 0.4 cm. Then, it is covered with the backing layer, cooled, and cut to size to obtain the external patch for analgesia, dampness removal, detoxification, and weight loss.

[0100] Example 2

[0101] This embodiment provides a formula for an external patch for analgesia, dampness removal, detoxification, and weight loss, which is composed of a backing layer, a plaster layer, and a non-stick layer. The plaster layer is formed by mixing the analgesic and dampness-removing components prepared in Preparation Example 5, the functionalized β-cyclodextrin prepared in Preparation Example 2, Tween-80, and genipin in a mass ratio of 14:9:2.2:3.0;

[0102] Step S1: After the hot-melt pressure-sensitive adhesive is heated and melted, the plaster layer is added, and then azone is added. After stirring, it is spread. Among them, the mass ratio of the hot-melt pressure-sensitive adhesive, the plaster layer, and azone is 950:170:50;

[0103] Step S2: The paste prepared in Step S1 is evenly coated on the non-stick layer, and the coating thickness is controlled to be 0.6 cm. Then, it is covered with the backing layer, cooled, and cut to size to obtain the external patch for analgesia, dampness removal, detoxification, and weight loss.

[0104] Example 3

[0105] This embodiment provides a formula for an external patch for analgesia, dampness removal, detoxification, and weight loss, which is composed of a backing layer, a plaster layer, and a non-stick layer. The plaster layer is formed by mixing the analgesic and dampness-removing components prepared in Preparation Example 6, the functionalized β-cyclodextrin prepared in Preparation Example 3, ascorbic acid, and genipin in a mass ratio of 16:10:2.4:3.2;

[0106] Step S1: After the hot-melt pressure-sensitive adhesive is heated and melted, the plaster layer is added, and then azone is added. After stirring, it is spread. Among them, the mass ratio of the hot-melt pressure-sensitive adhesive, the plaster layer, and azone is 1000:180:60;

[0107] Step S2: The paste prepared in Step S1 is evenly coated on the non-stick layer, and the coating thickness is controlled to be 0.8 cm. Then, it is covered with the backing layer, cooled, and cut to size to obtain the external patch for analgesia, dampness removal, detoxification, and weight loss.

[0108] Comparative Example 1

[0109] Comparative Example 1 was the same as Example 1, except that the functionalized β-cyclodextrin in Example 1 was replaced with the functionalized β-cyclodextrin prepared in Comparative Preparation Example 1.

[0110] Comparative Example 2

[0111] Comparative Example 2 was the same as Example 1, except that the functionalized β-cyclodextrin in Example 1 was replaced with the functionalized β-cyclodextrin prepared in Comparative Preparation Example 2.

[0112] Comparative Example 3

[0113] Comparative Example 3 was the same as Example 1, except that the analgesic and dampness-removing component in Example 1 was replaced with the analgesic and dampness-removing component prepared in Comparative Preparation Example 3.

[0114] Comparative Example 4

[0115] Comparative Example 4 was the same as Example 1, except that the analgesic and dampness-removing component in Example 1 was replaced with the analgesic and dampness-removing component prepared in Comparative Preparation Example 4.

[0116] Comparative Example 5

[0117] Comparative Example 5 was the same as Example 1, except that the analgesic and dampness-removing component in Example 1 was replaced with the analgesic and dampness-removing component prepared in Comparative Preparation Example 5.

[0118] 1. Therapeutic effect test

[0119] The therapeutic effects of the externally applied patches for analgesic, dampness-removing, detoxifying and weight loss prepared in Preparation Examples 1-3 of the present application and Comparative Examples 1-4 were tested respectively.

[0120] 1.1 Analgesic effect

[0121] The experimental animals were ICR mice with a body weight of 18-22 g provided by Shanghai Slack Experimental Animal Co., Ltd. (SCXK(Shanghai)2017-0005). The mice were placed at 18-22 °C, relative humidity: 60%-70%, light condition: 12 h / 12 h, light and dark alternation, and adaptively fed for one week.

[0122] 1.11 Hot plate experiment

[0123] Adjust the temperature of the intelligent hot plate instrument to (55 ± 0.1) °C, place the mice in the hot plate instrument, start the timer, cover the upper cover to prevent them from jumping out. Stop the timer and record when the mice show the reaction of licking their hind paws. The recorded value is the pain threshold of the mice. After measuring the pain thresholds of all mice, rest for two hours, and then repeat the measurement of the pain thresholds of each group of mice. Exclude the mice with the average pain threshold of the two times < 5 s and > 30 s. Randomly divide 100 qualified mice into groups according to the pain threshold, and set them as the blank control group, diclofenac control group, preparation examples 1 - 3 groups, and comparative preparation examples 1 - 5 groups, with 10 mice in each group. First, use a depilator and depilatory cream to depilate the back area of the mice. One day later, in the depilated area on the back of the mice, the blank control group was given a 2 cm 2 blank matrix patch, the diclofenac control group was given diclofenac rubbing at 1.0 ml / kg, and the preparation examples 1 - 3 and comparative preparation examples 1 - 5 groups were respectively applied with the prepared 2 cm 2 external patch. The administration frequency was once a day, and a total of two administrations were given. One hour / two hours / three hours after the last administration, measure the pain threshold of the mice once. Considering that the hind paws of the mice will briefly leave the hot plate when they jump, for every 4 jumps of the mice, subtract 1 s from the time. To prevent the mice from being scalded, if the mice do not lick their hind paws within 60 s in the hot plate instrument, the test can be stopped, take out the mice, and the pain threshold is counted as 60 s. All data were statistically analyzed using SPSS 25.0 software. Measurement data were expressed as , and t - test was used. P < 0.05 was considered statistically significant.

[0124] Table 1 Comparison of pain thresholds of mice in each group (n = 10, )

[0125] Project 1h 2h 3h Example 1 <![CDATA[22.581±3.283 d > <![CDATA[24.529±11.288 c > <![CDATA[32.637±11.657 c > Example 2 <![CDATA[24.756±3.537 a，d > <![CDATA[28.822±16.642 c > <![CDATA[37.794±16.282 b，d > Example 3 <![CDATA[23.465±3.359 d > <![CDATA[26.375±13.257 c > <![CDATA[34.268±13.346 b，d > Comparative Example 1 <![CDATA[18.526±3.757 b > 18.164±8.264 21.536±9.361 Comparative Example 2 <![CDATA[17.437±4.164 b > 19.175±5.163 18.094±6.356 Comparative Example 3 <![CDATA[19.346±3.651 b > 21.235±6.746 25.412±10.351 Comparative Example 4 <![CDATA[18.862±3.714 b > 20.107±5.837 23.742±9.433 Comparative Example 5 <![CDATA[20.147±3.345 b > 22.758±7.241 27.275±11.243 Voltaren Group 26.820±4.753b 18.257+5.203 20.738±8.497 Blank Control Group 16.755±2.683 19.256±8.153 14.258±5.731

[0126] Note: In Table 1, compared with the blank control group, aP < 0.05, b P < 0.05, compared with the model control group and the diclofenac control group, c P < 0.05, d P < 0.01.

[0127] 1.1.2 Acetic acid - induced pain writhing experiment in mice

[0128] Take 110 ICR female mice, group them according to body weight ranking, and set them as the blank control group, model control group, diclofenac control group, example 1 - 3 groups, and comparative example 1 - 5 groups, with 10 mice in each group. First, use a depilator and depilatory cream to depilate the back area of the mice. One day later, in the depilated area on the back of the mice, the blank control group and the model control group were given a 2 cm 2 blank matrix patch, the diclofenac control group was given diclofenac rubbing at 1.0 ml / kg, and the preparation examples 1 - 3 and comparative preparation examples 1 - 5 groups were respectively applied with the prepared 2 cm 2External patch, the administration frequency is once a day, and the administration is given twice in total. 1 hour after the last administration, the mice in the blank control group were intraperitoneally injected with 0.9% normal saline, and the rest of each mouse was intraperitoneally injected with 0.8% glacial acetic acid solution. The injection dose was 0.2 mL / mouse. At regular intervals of 20 minutes, the reactions of the mice were observed, the writhing times of the mice in each group were recorded, and the writhing inhibition rate of the mice in each group was calculated. The calculation formula is as follows, and the specific detection results are shown in Table 1:

[0129]

[0130] Table 2 Comparison of writhing times and writhing inhibition rates of mice in each group (n = 10, )

[0131] Project Number of Writhing Times / times Writhing Inhibition Rate / % Example 1 <![CDATA[19.3000±3.641 b > 52.73 Example 2 <![CDATA[17.1000±4.821 b > 58.11 Example 3 <![CDATA[18.5000±4.316 b > 54.69 Comparative Example 1 <![CDATA[32.000±2.457 b > 21.61 Comparative Example 2 <![CDATA[34.000±2.457 b > 16.72 Comparative Example 3 <![CDATA[30.000±2.457 b > 26.52 Comparative Example 4 <![CDATA[31.000±3.158 b > 24.07 Comparative Example 5 <![CDATA[29.000±2.635 b > 28.97 Voltaren Group <![CDATA[26.000±2.457 b > 36.32 Model Group <![CDATA[40.826±4.034 2 > / Blank Control Group 0 /

[0132] Note: In Table 2, compared with the blank control group, aP < 0.01, compared with the model control group b P < 0.01, compared with the diclofenac control group c P < 0.01.

[0133] It can be seen from Table 1 and Table 2 that compared with Comparative Examples 1-5, the external patches prepared in Examples 1-3 have more excellent analgesic effects.

[0134] 1.2 Dampness-removing and weight-loss effects

[0135] 1.21 Dampness-removing effect

[0136] Traditional Chinese medicine syndrome evaluation

[0137] According to the model establishment method disclosed in the literature "Chen Hao et al. 'Establishment and objective evaluation of a simple obesity animal model with spleen deficiency and dampness obstruction.' Journal of Jiangxi University of Traditional Chinese Medicine 31.6 (2019): 4.", 90 simple obesity rat models with spleen deficiency and dampness obstruction were established. The 90 qualified rats were randomly grouped and set as the blank control group, Examples 1-3 groups, and Comparative Examples 1-5 groups, with 10 rats in each group. First, the back area of the mice was depilated with a depilator and depilatory cream. 1 day later, on the depilated area of the mice's back, the blank control group was given a 2 cm 2 blank matrix patch, and the groups of Preparation Examples 1-3 and Comparative Preparation Examples 1-5 were respectively applied with the prepared 2 cm 2 external patch. The administration frequency is once every 2 days, 3 times a week for treatment, and 4 weeks is a treatment course. A total of 2 treatment courses were carried out. After the treatment, the following index evaluations were carried out;

[0138] 1. Self - developed Traditional Chinese Medicine Syndrome Scoring Scale (see Table 1): Referring to the "Diagnosis and Efficacy Evaluation Criteria for Simple Obesity" revised at the 5th National Academic Conference on Obesity Research in 1997, the total score was calculated based on the main clinical symptoms of simple obesity (spleen deficiency and dampness obstruction type) of Traditional Chinese Medicine. The specific evaluation scale is shown in Table 3, and the evaluation results are shown in Table 4.

[0139] Table 3 Traditional Chinese Medicine Syndrome Scoring Scale

[0140]

[0141] Table 4 Comparison of Traditional Chinese Medicine Syndrome Scores before and after Treatment

[0142]

[0143] Note: In Table 4, within - group comparison before and after treatment a P < 0.05, b P < 0.01, comparison between the two groups after treatment c P < 0.05, d P > 0.05.

[0144] As can be seen from Table 4, compared with Comparative Examples 1 - 5, the external patches prepared in Examples 1 - 3 have more excellent effects of dispelling dampness and detoxifying.

[0145] 1.22 Weight - loss effect

[0146] Measurement of body weight, BMI and body fat percentage

[0147] 2. Self - developed Efficacy Evaluation Criteria for Simple Obesity: Referring to the "Diagnosis and Efficacy Evaluation Criteria for Simple Obesity" revised at the 5th National Academic Conference on Obesity Research in 1997 and adjusted in combination with the characteristics of animal experiments, two or more of the obesity indicators are required to be met. According to the following evaluation criteria, the indicators of Examples 1 - 3, Comparative Examples 1 - 5 and the blank control group were measured in turn, and the evaluation results are shown in Table 5.

[0148] Table 5 Efficacy Evaluation Criteria for Simple Obesity

[0149] Clinical Symptoms Weight Loss Rate / % Clinical Cure Disappeared or Basically Disappeared ＞20 Marked Effect Mostly Disappeared or Basically Disappeared 10-20 Effective Significantly Alleviated 5-10 Ineffective No Obvious Improvement ＜5

[0150] Note: Weight loss: Based on the percentage value of the weight loss value at the end of the treatment course accounting for the difference between the actual weight and the standard weight.

[0151] Table 6 Comparison of body weight and less index before and after treatment

[0152]

[0153] Note: In Table 6, within - group comparison before and after treatment a P < 0.05, bP < 0.01, comparison between the two groups after treatment c P < 0.05, d P > 0.05.

[0154] As can be seen from Table 6, compared with Comparative Examples 1-5, the external patches prepared in Examples 1-3 have more excellent weight loss effects.

[0155] In the description of the specification, the descriptions referring to terms such as "one embodiment", "example", "specific example", etc. mean that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0156] This specific embodiment is only an interpretation of the present application and is not a limitation to the present application. Those skilled in the art can make modifications without creative contributions to this embodiment according to needs after reading this specification, but as long as it is within the scope of the claims of the present application, it is protected by the patent law.

Claims

1. A prescription for an external patch for relieving pain, removing dampness, detoxifying and reducing weight, characterized in that: It is composed of a hot-melt pressure-sensitive adhesive, a plaster layer, a transdermal absorption accelerator, a backing layer, a plaster layer and an anti-adhesive layer, wherein the plaster layer is mixed with analgesic and dehumidifying ingredients, functionalized β-cyclodextrin, a stabilizer and a cross-linking agent in a mass ratio of 12-16:8-10:2.0-2.4:2.8-3.2; The functionalized β-cyclodextrin is firstly prepared by reacting β-cyclodextrin with octenyl succinic anhydride through a ring-opening esterification reaction to obtain modified β-cyclodextrin, and then reacting it with p-aminosalicylic acid through an amidation reaction to obtain phenylated β-cyclodextrin, and finally mixing it with a bamboo charcoal alcohol solution to obtain the functionalized β-cyclodextrin; The analgesic and dehumidifying component includes a raw material drug and a matrix, and the raw material drug is composed of the following raw materials in parts by weight: 30-50 parts of salvia miltiorrhiza, 24-28 parts of angelica dahurica, 22-27 parts of plantain, 18-24 parts of atractylodes, 16-22 parts of kadzu vine, 20-25 parts of lotus leaf, 11-13 parts of mint, 12-14 parts of myrrh, 5-9 parts of scutellaria baicalensis and 6-8 parts of seaweed; The matrix comprises 600-800 parts of sesame oil and 70-90 parts of xanthan gum.

2. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 1, characterized in that: The preparation method of the analgesic and dehumidifying component comprises the following steps: Step A1, grinding plantain, atractylodes, cyperus rotundus, lotus leaf, mint, myrrh, radix spatholobi and seaweed together to obtain a mixed powder; Step A2, taking 50-80% of the mixed powder by weight, extracting with anhydrous ethanol and deionized water in turn, concentrating, drying and pulverizing to obtain a mixed extract; Step A3, simmer sesame oil to 120-140°C, add xanthan gum, turn off the heat after the xanthan gum melts, add salvia miltiorrhiza powder and the remaining mixed powder while stirring, continue stirring until the system temperature is below 40°C, add angelica dahurica powder and the mixed extract, mix evenly, cool, and obtain the analgesic and dampness-relieving component.

3. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 1, characterized in that: The functionalized β-cyclodextrin is prepared by the following steps: Step B1, adding β-cyclodextrin to N,N-dimethylformamide, stirring evenly at 35-45° C., adjusting the pH value to 9-11, dropping a mixed solution a of octenyl succinic anhydride and isopropanol, raising the temperature to 85-95° C., continuing to stir and react for 4-6 hours, adjusting the pH value to 6-7, washing, recrystallizing, and drying to obtain modified β-cyclodextrin; Step B2, dissolving the modified β-cyclodextrin and para-aminosalicylic acid in anhydrous DMF, raising the temperature to 42-46°C, adding a mixture of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF dropwise while stirring, raising the temperature to 72-78°C, stirring and reacting for 3-5 hours, after the reaction is completed, filtering, washing and drying to obtain phenylated β-cyclodextrin, adding the phenylated β-cyclodextrin to anhydrous DMF, ultrasonically dispersing it evenly, adding the bamboo charcoal alcohol solution, stirring and mixing for 14-16 hours, centrifuging, precipitating, washing and drying to obtain functionalized β-cyclodextrin.

4. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 3, characterized in that: In the step B1, the mass ratio of β-cyclodextrin, N,N-dimethylformamide and mixed solution a is 3-6:50-60:0.8-1.

2.

5. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 3, characterized in that: In the mixed solution a, the mass ratio of octenyl succinic anhydride to isopropanol is 1-2:10-20.

6. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 3, characterized in that: In the step B2, the mass ratio of modified β-cyclodextrin, p-aminosalicylic acid, anhydrous DMF and mixed solution b is 5-7: 0.2-0.4: 60-70: 30-40.

7. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 3, characterized in that: In the mixed solution b, the mass ratio of N,N-dicyclohexylcarbodiimide, 4-dimethylaminopyridine and anhydrous DMF is 0.8-1.2:0.54-0.66:16-20, and the mass ratio of phenylated β-cyclodextrin, anhydrous DMF and bamboo charcoal alcohol solution is 4-5:46-50:26-32.

8. The external-use patch formula for relieving pain, removing dampness, detoxifying and reducing weight according to claim 3, characterized in that: The bamboo charcoal alcohol solution is prepared by ultrasonically dispersing bamboo charcoal powder and ethanol aqueous solution in a mass ratio of 1:12-16, and the mass fraction of the ethanol aqueous solution is 20-50%.

9. A method for preparing the analgesic, dehumidifying, detoxifying and weight-reducing external patch according to any one of claims 1 to 8, characterized in that: The following steps are involved: Step S1, after the hot melt pressure sensitive adhesive is heated and melted, a plaster layer is added, and then a transdermal absorption enhancer is added, and the mixture is stirred and spread to obtain a paste; Step S2, evenly coating the paste obtained in step S1 on the anti-adhesive layer, and then covering it with a backing layer, cooling it, and cutting it into size to obtain an external patch for relieving pain, removing dampness, detoxifying and reducing weight.

10. A method for preparing the analgesic, dehumidifying, detoxifying and weight-reducing external patch according to claim 9, characterized in that: In the step S1, the mass ratio of the hot melt pressure-sensitive adhesive, the plaster layer and the transdermal absorption enhancer is 900-1000:160-180:40-60.

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